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慢性脑低灌注大鼠 NSTyr 对认知功能和神经元可塑性的神经保护作用。

Neuroprotective effects of NSTyr on cognitive function and neuronal plasticity in rats of chronic cerebral hypoperfusion.

机构信息

Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

出版信息

Brain Res. 2010 Apr 14;1325:183-90. doi: 10.1016/j.brainres.2010.02.037. Epub 2010 Feb 16.

DOI:10.1016/j.brainres.2010.02.037
PMID:20167210
Abstract

The neuroprotective effects of N-stearoyl-L-tyrosine (NSTyr) on cognitive function and neuronal plasticity during chronic cerebral hypoperfusion (CCH) in rats were investigated. After induction of CCH, NSTyr was administered daily for 3 months intraperitoneally. Cognitive functions were evaluated by Morris water maze and hippocampal long-term potentiation (LTP). Neuropathological changes were examined using light micrograph and Fluoro-Jade B staining. Neuronal plasticity was assessed by measuring the expression of MAP-2, GAP-43 and synaptophysin on hippocampal regions of rats with immunohistochemistry and western blotting. CCH resulted in significant spatial memory impairment and inhibition of LTP, and led to neurodegeneration in the CA1 region of the hippocampus in the model rats compared with the sham-operated rats. In the model rats treated with NSTyr, cognitive function improved. The expression levels of MAP-2 and synaptophysin protein in hippocampal areas in the model rats were less than those in the sham-operated rats, and increased in the model rats treated with NSTyr. However, no statistical significance of GAP-43 expression among the sham, model and NSTyr groups was observed. These data indicate that NSTyr exerts protective effects on cognitive function of rats after CCH, which may be related to the changes of neurodegeneration and neuronal plasticity in the hippocampal area of rats.

摘要

研究了 N-硬脂酰-L-酪氨酸(NSTyr)对慢性大脑低灌注(CCH)大鼠认知功能和神经元可塑性的神经保护作用。在诱导 CCH 后,通过腹腔内每日给予 NSTyr 治疗 3 个月。通过 Morris 水迷宫和海马长时程增强(LTP)评估认知功能。使用光显微镜和 Fluoro-Jade B 染色检查神经病理学变化。通过免疫组织化学和 Western blot 测量海马区域中 MAP-2、GAP-43 和突触小体蛋白的表达来评估神经元可塑性。与假手术组大鼠相比,CCH 导致模型大鼠海马 CA1 区出现明显的空间记忆障碍和 LTP 抑制,并导致神经退行性变。在接受 NSTyr 治疗的模型大鼠中,认知功能得到改善。模型大鼠海马区域中 MAP-2 和突触小体蛋白的表达水平低于假手术组大鼠,而接受 NSTyr 治疗的模型大鼠则增加。然而,在假手术组、模型组和 NSTyr 组之间,GAP-43 表达无统计学意义。这些数据表明,NSTyr 对 CCH 后大鼠的认知功能具有保护作用,这可能与大鼠海马区神经退行性变和神经元可塑性的变化有关。

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